Peritoneal dialysis: changes to the structure of the peritoneal membrane and potential for biocompatible solutions

Peritoneal dialysis (PD) is now established as a viable and successful alternative to hemodialysis (HD) for patients starting on renal replacement therapy. A number of studies have confirmed that equivalent adequacy and fluid balance are provided at least for the first four to five years of renal replacement therapy (RRT). Loss of peritoneal membrane function remains a major factor leading to treatment failure in a significant number of patients on PD. Numerous studies have suggested a relationship between these changes in function and structural changes in the membrane. A careful analysis of peritoneal biopsies from PD patients would allow the clear identification of those changes unique to PD, in addition to indicating possible correlations with glucose exposure as well as other functional parameters.

We systematically examined peritoneal biopsies from 13 normal individuals, 29 uremic predialysis patients, 55 HD patients, and 157 patients on long-term PD. Well-oriented specimens were stained with toluidine blue and examined by a blinded pathologist. Limited clinical data has allowed a preliminary analysis of structure-function relationships.

The median thickness of the submesothelial compact collagenous zone was 40 microm in normal individuals, 150 microm in uremic patients, 150 microm in patients on HD, and 2550 microm in patients on PD (P < 0.001 for all vs. normal individuals). Compact zone thickness increased significantly with duration of PD therapy (0 to 24 months, 180 microm;>97 months, 600 microm). Vascular changes comprised progressive subendothelial hyalinization of postcapillary venules, with luminal narrowing or obliteration. These changes were present in uremic patients and increased significantly with PD duration (P = 0.0001).

These data indicate that morphologic changes in the postcapillary venules and the submesothelial compact zone of PD patients begin during the uremic phase of their illness. This is then worsened by time spent on PD. The relationships with glucose exposure or glucose degradation products have yet to be established.